TIL adoptive cell therapy (autologous) delivers 22% ORR in metastatic uveal melanoma—responses track with UMIS-selected, tumor-reactive products

Autologous tumor-infiltrating lymphocyte (TIL) adoptive cell therapy—generated from resected metastases, expanded ex vivo, then given after cyclophosphamide/fludarabine lymphodepletion with high-dose IL-2—was tested in a single-center Phase 2 study in heavily pretreated metastatic uveal melanoma (NCT03467516). In 32 evaluable patients (n=33 treated; median 2 prior lines; 64% prior checkpoint blockade; 33% prior tebentafusp; 76% elevated LDH; 24% CNS disease), ORR was 22% (7/32) with median duration of response 10.8 months (max ongoing 58 months); by comparison, published benchmarks in this disease are typically low for immunotherapy—tebentafusp has a modest ORR (often ~7–10% despite OS benefit in HLA-A*02:01+ patients) and ipilimumab+nivolumab is commonly ~10–20% ORR across series/trials. Product potency was the differentiator: tumor-reactive TIL products had 37% ORR (7/19) vs 0% (0/12) for nonreactive (P=0.026), with higher peripheral persistence of infused clones in responders (R/NR ratio 10.69, P=0.020); in a pooled dataset (n=54; 52 evaluable), reactive products drove 43% ORR (12/28) vs 0% (0/20) (P=5.06E-4). The in situ transcriptomic biomarker UMIS predicted tumor-reactive culture growth (rho=0.55, P=2.72E-5), final product reactivity (P=0.040), and clinical response (P=0.004), suggesting a practical way to “pick the right lesion” for harvest when multiple metastases exist.